title: MiR-205 is downregulated in hereditary hemorrhagic telangiectasia and impairs TGF-beta signaling pathways in endothelial cells.
abstract: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by arteriovenous malformations and hemorrhages. This vascular disease results mainly from mutations in 2 genes involved in the TGF-β pathway (ENG and ALK1) that are exclusively expressed by endothelial cells. The present study identified miR-27a and miR-205 as two circulating miRNAs differentially expressed in HHT patients. The plasma levels of miR-27a are elevated while those of miR-205 are reduced in both HHT1 and HHT2 patients compared to healthy controls. The role of miR-205 in endothelial cells was further investigated. Our data indicates that miR-205 expression displaces the TGF-β balance towards the anti-angiogenic side by targeting Smad1 and Smad4. In line, overexpression of miR-205 in endothelial cells reduces proliferation, migration and tube formation while its inhibition shows opposite effects. This study not only suggests that detection of circulating miRNA (miR-27a and miR-205) could help for the screening of HHT patients but also provides a functional link between the deregulated expression of miR-205 and the HHT phenotype.
authors.affiliation: Unit of Molecular Biology and Genetic Engineering, GIGA, University of Liège, Sart-Tilman, 4000, Liège, Belgium.
authors.forename: Sebastien P
authors.initials: SP
authors.lastname: Tabruyn
authors.forename: Sylvain
authors.initials: S
authors.lastname: Hansen
authors.forename: Maria-Luisa
authors.initials: ML
authors.lastname: Ojeda-Fernández
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bovy
authors.forename: Roberto
authors.initials: R
authors.lastname: Zarrabeitia
authors.forename: Lucia
authors.initials: L
authors.lastname: Recio-Poveda
authors.forename: Carmelo
authors.initials: C
authors.lastname: Bernabéu
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Martial
authors.forename: Luisa-Maria
authors.initials: LM
authors.lastname: Botella
authors.forename: Ingrid
authors.initials: I
authors.lastname: Struman
mesh_terms: D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D055785:Gene Knockdown Techniques; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010641:Phenotype; D012372:ROC Curve; D018125:Receptors, Transforming Growth Factor beta / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D051898:Smad1 Protein / Q000096:biosynthesis / Q000235:genetics; D051901:Smad4 Protein / Q000096:biosynthesis / Q000235:genetics; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D059467:Transcriptome; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*
chemical_list: D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D018125:Receptors, Transforming Growth Factor beta; D051898:Smad1 Protein; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta; C534425:MIR205, human; C531388:MIRN27 microRNA, human; C497399:SMAD1 protein, human; C497796:SMAD4 protein, human